UNASSIGNED: MELAS is a disorder with clinical variability that also responsible for a significant portion of unexplained hereditary or childhood-onset hearing loss. Although patients typically present in childhood, the first stroke-like episode can occur later in life in some patients, potentially related to a lower heteroplasmy level. It is crucial to consider MELAS as a potential cause of stroke-like events if age at presentation and symptoms are atypical, especially among middle-aged patients without vascular risk factors.
UNASSIGNED: MELAS syndrome (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) is a rare genetic condition that most patients develop stroke-like episodes before the age of 40. We report a 52-year-old female with a documented 40-year history of progressive sensorineural hearing loss, developed a visual field deficit and stroke-like events in her middle age who finally diagnosed was MELAS. The patient was started on vitamin E, l-carnitine, l-arginine, and coenzyme Q10 that gradually improved before dismissal from the hospital. This case highlights the importance of considering MELAS as a potential cause of stroke-like events if imaging findings are atypical for cerebral infarction, especially among middle-aged patients without vascular risk factors and an unusual cause of progressive sensorineural hearing loss.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a maternally inherited multisystemic disorder caused by mutations in mitochondrial DNA that result in cellular energy deficiency. MELAS affects the most metabolically active organs, including the brain, skeletal muscles, cochlea, retina, heart, kidneys, and pancreas. As a result, about 85% of carriers of m.3243A > G, the most common mutation in MELAS, develop diabetes by the age of 70. Although metformin is the most widely prescribed drug for diabetes, its usefulness in mitochondrial dysfunction remains controversial. Here, we present the case of a 32-year-old Korean patient diagnosed with MELAS who presented with exacerbated stroke-like episodes and lactic acidosis triggered by metformin.

BACKGROUND: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a subset of rare mitochondrial diseases characterized by diverse clinical manifestations, which often complicates its diagnosis.
METHODS: This report chronicles the experiences of a 14-year-old female patient who underwent multiple misdiagnoses before the eventual identification of MELAS syndrome. Her journey began with symptoms that included growth retardation, hypertrophic cardiomyopathy, and epilepsy.
METHODS: The definitive diagnosis of MELAS syndrome was established through genetic confirmation, revealing a mutation in the MT-TL1 gene (m.3242A > G).
METHODS: Upon diagnosis, the patient received targeted symptomatic treatment, which led to pronounced improvements in her symptoms.
RESULTS: The patient\'s condition stabilized with the administered treatments, and she exhibited significant symptom relief, emphasizing the importance of accurate diagnosis and timely intervention.
CONCLUSIONS: This case underscores the imperative for heightened clinical vigilance and thorough differential diagnosis in the face of complex clinical presentations, such as those seen in MELAS syndrome, to ensure timely and appropriate interventions.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a complex and infrequently encountered mitochondrial cytopathy. Patients with MELAS often present with multi-systemic manifestations, making their anesthetic management particularly challenging. In this case report, we describe in detail our anesthetic approach for a 19-year-old male with confirmed MELAS linked to an m.3243A>G mutation. The patient had been diagnosed with MELAS at age 12 following a stroke-like episode and presented with progressive spinal deformities. He exhibited a 70° thoracic spine curvature and an 80° kyphosis, requiring a T1-L2 posterior spinal fusion. The surgical plan included neuromonitoring with both somatosensory and motor evoked potentials. Intravenous anesthetics such as propofol are typically preferred in this context due to their reduced interference with neuromonitoring compared to volatile anesthetics. Anticipating a surgical duration of six to seven hours, however, we hesitated to rely on propofol for this extended period due to its potential risks of lactic acidosis in the context of MELAS. Given that propofol infusion for extended periods (>48 hours) or at high doses (≥5 mg·kg-1·hour-1) is known to induce propofol-related infusion syndrome, and coupled with our concerns about the risk of lactic acidosis in this patient, we were compelled to design an anesthetic plan that avoided propofol altogether without excessive use of volatile anesthetics. This proactive approach ensured the maintenance of consistent neuromonitoring signals and the patient\'s safety, especially given his underlying mitochondrial dysfunction. Our primary rationale in presenting this case report is to highlight the challenges posed by MELAS in the setting of extended surgery, with a focus on anesthetic considerations during neuromonitoring. For prolonged surgeries that typically rely heavily on intravenous anesthetics, which interfere less with neuromonitoring than volatile anesthetics, the use of propofol should be approached with caution in MELAS contexts due to its associated risk of lactic acidosis. To our knowledge, this is the first case report that described the anesthetic management of a patient with MELAS undergoing a procedure of such duration, requiring both somatosensory and motor evoked potential neuromonitoring. We believe our experiences will serve as a reference for anesthesiologists and perioperative teams faced with similar challenging clinical situations.

UNASSIGNED: Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder caused by mutations in mitochondrial DNA, resulting in impaired energy production and affecting multiple organs. We present a suspected MELAS syndrome case with the initial symptom of chest tightness.
UNASSIGNED: A 46-year-old man sought medical attention due to progressively worsening chest tightness during physical activity. He had been receiving treatment for type 2 diabetes for 15 years. One year ago, he presented with symptoms of hearing impairment. Transthoracic echocardiography revealed increased thickness of the left ventricular wall. Serum protein electrophoresis showed no evidence of light-chain amyloidosis, and the 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scan showed no definite uptake in the heart muscle. The patient\'s head magnetic resonance imaging (MRI) indicated lacunar infarcts. The lactate threshold test was positive. The biopsy of the skeletal muscle showed broken red fibre infiltration on modified Gomori trichrome staining, and electron microscopy revealed signs of mitochondrial cardiomyopathy, including mild mitochondrial swelling, lipid accumulation, and myofibril damage. A whole-exome genetic test was used to detect the m.3243A>G mutation in the MT-TL1 gene. Based on these findings, MELAS syndrome was the most probable diagnosis.
UNASSIGNED: The patient presented with chest tightness in adulthood, without any accompanying psychoneurological symptoms. However, the patient presented with other symptoms, including diabetes mellitus, hearing loss, abnormal lactate levels, ischaemic lesions on head MRI, and left ventricular hypertrophy. By identifying a mutation in the MT-TL1 gene and conducting a muscle biopsy, the diagnosis of MELAS syndrome was definitively confirmed.

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BACKGROUND: Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is the most common subtype of mitochondrial encephalopathy. In the past, it was believed that most hereditary white matter lesions were lysosome storage disorders or peroxisome diseases. However, in recent years, white matter lesions have been increasingly regarded as a common feature of patients with mitochondrial diseases. In addition to stroke-like lesions, about half of the patients with MELAS reported white matter lesions in the brain.
METHODS: Herein, we provide a case of A 48-year-old female who presented with episodic loss of consciousness with twitching of extremities. Previous medical history revealed 10 years of history of epilepsy, 10 years of history of diabetes, a history of hearing loss, and unknown etiology. Ancillary findings included brain magnetic fluid-attenuated inversion recovery showed symmetrical lesions in the bilateral parietal lobe with high signal intensity at the edge, and high signal intensity in the bilateral occipital lobe, paraventricular white matter, corona radiata, and the center of semiovale.
METHODS: Mitochondrial deoxyribonucleic acid gene sequencing returned A3243G point mutation and it supports the diagnosis of intracranial hypertension.
METHODS: Considered the diagnosis of symptomatic epilepsy, the patient was treated with mechanical ventilation, midazolam, and levetiracetam, and the limb twitching symptoms were controlled. The patient was comatose, chronically bedridden, with gastrointestinal dysfunction, and was treated prophylactically with antibiotics against infection, parenteral nutrition, and other supportive measures. B vitamins, vitamin C, vitamin E, coenzyme Q10, and idebenone were given, and mechanical ventilation and midazolam were stopped after 8 days. He was discharged from the hospital on 30 days and continued symptomatic treatment with B-vitamins, vitamin C, vitamin E, coenzyme Q10, and idebenone, and antiepileptic treatment with levetiracetam, with outpatient follow-up.
RESULTS: No further seizures were recorded and the patient recovered well.
CONCLUSIONS: MELAS syndrome without stroke-like episodes of diffuse posterior cerebral white matter lesions is rare in clinical practice, and the possibility of MELAS syndrome should be considered in symmetric posterior cerebral white matter lesions.

A biopsy of gastrocnemius muscle from a patient with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome was studied histologically in semithin sections stained by hematoxylin-and-eosin (H&E) and toluidine blue, and ultrathin sections by transmission electron microscopy (TEM). H&E stain demonstrated typical ragged-red fibers (RRFs) and affected fibers in fascicles. Toluidine-blue stain showed an irregular meshwork in the center of RRFs. TEM demonstrated damaged myofibrils and variations in mitochondrial structure in RRFs and affected fibers. Dense mitochondria were compacted with cristae and pleomorphic electron-dense inclusions. Lucent mitochondria included paracrystalline inclusions with a parking lot appearance. At high magnification, the paracrystalline inclusions were composed of plates that paralleled and connected with mitochondrial cristae. These observations indicated that electron-dense granular and paracrystalline inclusions resulted from cristal degeneration and overlapping in mitochondria in MELAS syndrome.

We discuss the involvement of nuclear genetic variants correlating to observed phenotype in this case study. In January 2020, the 19-year-old boy from Nantong, Jiangsu Province, China with epilepsy symptom was identified to have myelin loss in the motor and sensory nerves in the electromyogram examination. Brain magnetic resonance imaging (MRI) demonstrated high-intensity areas of small multifocal gray matter regions in the bilateral temporal, parietal, and occipital lobes. In the serum of the patient, the levels of lactate dehydrogenase (LDH) and lactic acid were higher than the normal range values in multiple tests. By subsequent whole exome sequencing (WES) including analysis of the mitochondrial genome, the patient was revealed to carry an m.3243A>G mutation in mitochondria MTTL1 gene which was confirmed by direct Sanger sequencing analysis. Thus, disease of the patient was diagnosed as mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. According to WES analysis, the patient also carried multiple homozygous variants, which correlating to myelinloss and epilepsy in nuclear genes. The peripheral neuropathy of the patient carrying single mitochondrial m.3243A>G mutation could be caused by multiple nuclear DNA defect.

UNASSIGNED: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a multi-organ disorder resulting from mitochondrial DNA (mtDNA) mutations. We report a case of suspected MELAS syndrome that progressed to left ventricular dysfunction 24 years after an initial diagnosis of atrioventricular block (AVB).
UNASSIGNED: A 51-year-old woman was referred to heart failure clinic because of dyspnoea on exertion and progressive cardiomegaly. She had a dual-chamber pacemaker implanted for 24 years because of a high-degree AVB. She was treated for diabetes mellitus for 23 years and used hearing aids for 12 years because of sensorineural hearing loss. Transthoracic echocardiography revealed reduced left ventricular ejection fraction (26%), with increased thickness and unusual texture of the myocardium. The absence of abnormal findings on serum and urine protein electrophoresis suggested that light-chain amyloidosis was unlikely. In addition, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy revealed no definite uptake in the myocardium. Endomyocardial biopsy revealed a hypertrophy of myocytes in haematoxylin-eosin staining, and electron microscopy revealed a disarrangement of mitochondrial cristae, which were suggestive of mitochondrial cardiomyopathy. A mtDNA test detected the m.3243A > G mutation in the MT-TL1 gene. According to these findings, MELAS syndrome was the most probable diagnosis despite the absence of common symptoms such as stroke-like episodes or lactic acidosis.
UNASSIGNED: The patient had progressed to heart failure with reduced ejection fraction 24 years after the first cardiac manifestation. An identification of the mutation in the MT-TL1 gene, indicative of MELAS syndrome, enabled the diagnosis of MELAS syndrome without typical manifestations.